DESCRIPTION: This proposal intends to apply recent advances in the synthesis of new molecular scaffolds to several problems in molecular recognition. The new, cleft-shaped structures offer roomy interiors which can be functionalized along their concave linings with a variety of chemical surfaces. The functional groups converge to present acidic, basic and hydrophobic sites to smaller, convex shaped targets of interest. The availability of both lipophilic and hydrophilic derivatives will permit studies under a range of conditions. Specific problems to be addressed are the intermolecular forces of nitrogen-halogen interactions in solution, and the energetics of low barrier hydrogen bonds. In addition, the clefts will be used for asymmetric protonation and epoxidation reactions, the binding of metals in new ligand environments, and in combinatorial approaches to peptide recognition. By applying these methods to molecular recognition, it is hoped that introducing randomness to host design can give opportunities for the discovery of new, tight-binding complexes and molecular interactions that are unexpected or not well understood. By making these scaffolds known and accessible, it is expected that research in other areas of molecular recognition will be stimulated.